Figure 4

FORCE dependence on BOND DISSOCIATION probability and force dependence on bond dissociation rates. (A) Shown is the relationship between bondforce and probability of BOND DISSOCIATION for each of the three LIGAND pairs within the CONTACT ZONE. The effects of shear on the ligand-ligand bonds that form at the rear of the leukocyte are simulated using bondforce. BONDS within the rear row of the CONTACT ZONE experience a bondforce that is calculated by dividing the RearForce, a unitless parameter representing the effects of shear, by the total number of BONDS within the rear row. During a simulation cycle, each MEMBRANE UNIT in the rear row uses the current value of bondforce and the graphed relationship to calculate a probability that each BOND will be broken during that cycle. All BONDS elsewhere within the CONTACT ZONE experience a bondforce value of 0. UNSTRESSED (bondforce value of 0) DISSOCIATION probabilities for PSGL1/PSELECTIN, LOW-AFFINITY VLA4/VCAM1, and HIGH-AFFINITY VLA4/VCAM1 were chosen to be 0.14, 0.16, and 0.0035, respectively. (B) The in vitro force dependence of dissociation rates for P-selectin/PSGL-1 bonds (as reported in [15]) and the high affinity VLA-4/VCAM-1 bonds (as reported in [29]) are plotted for comparison to the analogue relationships in A. The plotted values were taken from the fitted in vitro data: see Methods for details. The relationships in A are analogues of these experimentally determined relationships and are not meant to either match or fit that data. The dissociation rates of the PSGL-1/P-selectin bonds as a function of force were determined by experiments using PSGL-1-coated microbeads rolling on a P-selectin substrate in a parallel plate flow chamber [15]. The dissociation rates for the VLA-4/VCAM-1 complex, described in Methods, were calculated from data obtained using single-molecule dynamic force spectroscopy [29]. The force dependence of dissociation rates for low affinity VLA-4/VCAM-1 data was not reported. We assumed that it is similar to PSGL-1/P-selectin relationship in A.